Enzyme kinetic parameters and estimated contribution ratio for each P450 isoform involved in the formation of M-1 and R-125528 For M-1 and R-125528 formation, final concentrations of 7.8 to 250 μM pactimibe were incubated for 30 min.
Metabolism | P450 isoform | Km | Vmax | CLint | Contentsa | Contributionb |
|---|---|---|---|---|---|---|
| μM | pmol/min/pmol P450 | μl/min/pmol P450 | pmol/mg | % | ||
| P | ||||||
| M-1 formation | CYP2C9 | 123.1 | 0.16 | 0.001 | 96 | 5.2 |
| CYP2C19 | 210.2 | 5.5 | 0.026 | 19 | 27 | |
| CYP2D6 | 25.1 | 3.1 | 0.124 | 10 | 67.8 | |
| R-125528 formation | CYP2C19 | 869.3 | 0.72 | 0.001 | 19 | 0.5 |
| CYP2D6 | 683.4 | 1.1 | 0.002 | 10 | 0.5 | |
|
| CYP3A4 | 26.8 | 1.0 | 0.037 | 108 | 99 |